rs17744121

Positions:

• chr21-29341277-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001186.4(BACH1):​c.1777-1122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 152,346 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.034 (121 hom., cov: 32)
• Consequence: BACH1 NM_001186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542

Genes affected

BACH1 (HGNC:935): (BTB domain and CNC homolog 1) This gene encodes a transcription factor that belongs to the cap'n'collar type of basic region leucine zipper factor family (CNC-bZip). The encoded protein contains broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domains, which is atypical of CNC-bZip family members. These BTB/POZ domains facilitate protein-protein interactions and formation of homo- and/or hetero-oligomers. When this encoded protein forms a heterodimer with MafK, it functions as a repressor of Maf recognition element (MARE) and transcription is repressed. Multiple alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, May 2009]

BACH1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACH1	NM_001186.4	c.1777-1122A>G		intron_variant		ENST00000286800.8	NP_001177.1
BACH1	NM_206866.3	c.1777-1122A>G		intron_variant			NP_996749.1
BACH1	NR_027655.3	n.1956-10357A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000286800.8	c.1777-1122A>G		intron_variant		1	NM_001186.4	ENSP00000286800.3
BACH1	ENST00000399921.5	c.1777-1122A>G		intron_variant		1		ENSP00000382805.1
BACH1	ENST00000422809.5	c.471+11584A>G		intron_variant		5		ENSP00000416569.1
BACH1	ENST00000468059.1	c.324+11584A>G		intron_variant		3		ENSP00000470673.1

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5245 AN: 152228 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0404

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0344 AC: 5248 AN: 152346 Hom.: 121 Cov.: 32 AF XY: 0.0322 AC XY: 2399 AN XY: 74500

Gnomad4 AFR AF: 0.0106

Gnomad4 AMR AF: 0.0269

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0182

Gnomad4 FIN AF: 0.0404

Gnomad4 NFE AF: 0.0554

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0479 Hom.: 173

Bravo AF: 0.0320

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17744121; hg19: chr21-30713598;